两种不同类型的胃癌组织中DNA氧化损伤的水平及临床意义

目的检测胃腺癌、印戒细胞癌组织及正常胃黏膜组织中8-羟基脱氧鸟苷（8- oxodGsn）水平，探讨DNA氧化损伤与不同类型胃癌临床指标间的关系。方法提取42例胃癌（腺癌28例，印戒细胞癌14例）及癌旁5cm以外的正常组织的DNA，并采用核酸酶P1和碱性磷酸酶消化成单个核苷，再采用高效液相色谱-串联质谱法（LC- MS/MS）检测其8- oxodGsn的水平；同时联合免疫组化法对组织中的8- oxodGsn进行定位分析。结果不同类型胃癌组织与正常组织中8- oxodGsn水平的差异均有统计学意义（均P＜0.05）。8- oxodGsn主要分布于肿瘤细胞的细胞质和细胞核内，腺癌细胞中以细胞核分布居多，印戒细胞癌中以细胞质分布居多。不同类型胃癌组织中8- oxodGsn水平在癌组织浸润深度、淋巴结转移程度、远处器官转移程度、临床病理分期等差异均有统计学意义（均P＜0.05）。结论8- oxodGsn水平在两种类型的胃癌组织中均有不同程度的增加，提示DNA氧化损伤可能是胃癌发生、发展的重要因素。

8-oxodGsn levels in gastric adenocarcinoma and signet ring cell carcinoma

Objective To investigate oxidative DNA damage in gastric adenocarcinoma, signet ring cell carcinoma and normal gastric mucosa by detecting 8- dihydro- 2＇- deoxyguanosine （8- oxodGsn） levels. Methods Specimens of gastric cancer tissues and normal gastric mucosa were obtained from 28 cases of adenocarcinoma and 14 cases of signet ring cel car-cinoma. The DNA was extracted from tissue specimens and digested by nuclease P1 and alkaline phosphatase. The levels of 8- oxodGsn were determined by LC- MS/MS method and the expression of 8- oxodGsn in tissue was detected by immunohisto-chemical method. Results There was a significant difference in 8- oxodGsn levels between gastric cancer and normal gastric mucosa（P〈0.05）. Immunohistochemical staining showed that 8- oxodGsn was mainly distributed in nucleus in gastric adenocar-cinoma, while mainly in cytoplasm in signet ring cel carcinoma. The expression levels of 8- oxodGsn were significantly correlated with invasion depth, lymph node metastasis, distant metastasis and clinical staging of gastric cancer （al P〈0.05）. Conclusion 8- oxodGsn levels are increased in gastric adenocarcinoma and gastric signet ring cel carcinoma in different extend, which sug-gested that oxidative DNA damage may be an important factor in the development of gastric cancer.